Exogenous Sonic hedgehog protein does not rescue cultured intestine from atresia formation.
Exogenous Sonic hedgehog protein does not rescue cultured intestine from atresia formation.
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DOI：
10.1016/j.jss.2013.11.1114
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发表时间：
2014-03
影响因子：
2.2
通讯作者：
Nichol, Peter F.
中科院分区：
文献类型：
--
作者：
Reeder, Amy L.;Zaremba, Krzysztof M.;Liebl, Rebeca M.;Kowalkowski, Anna;Nichol, Peter F.
肠闭锁形成的机制仍不明确。在Fgfr 2 IIIb −/−突变小鼠胚胎中，闭锁发生之前是内胚层凋亡和周围中胚层退化。我们已经观察到，闭锁段的退化是通过内胚层中的Sonic hedgehog（SHH）的下调进行的，内胚层是肠中胚层的关键组织者。我们假设在闭锁形成之前用外源性SHH蛋白补充Fgfr 2 IIIb −/−肠道可以防止中胚层退化并挽救正常的肠道发育。在胚胎（E）第11.5天和E12.0天之间，对对照和Fgfr 2 IIIb −/−肠道进行Shh或FoxF 1的原位杂交。在E10.5收获对照和Fgfr 2 IIIb −/−肠道，并在补充有FGF 10 + SHH或FGF 10与SHH包被珠的培养基中培养。在E12.5时对Foxf 1进行原位检查。Shh和Foxf 1表达在肠闭锁形成过程中下调。含有外源性FGF 10 + SHH的培养基不能防止结肠闭锁形成（退化）。SHH蛋白点源珠在对照和突变体中诱导Foxf 1表达。Shh和Foxf 1表达在远端结肠闭锁形成中被破坏，从而作为闭锁事件的潜在标志物。外源性SHH的应用（在培养基补充剂或作为点源珠）足以诱导Foxf 1表达，但不足以挽救Fgfr 2 IIIb −/−突变胚胎中远端结肠中胚层的发育。Shh信号中断不是Fgfr 2 IIIb功能丧失导致闭锁形成的关键机制。
The mechanism of intestinal atresia formation remains undefined. Atresia in Fgfr2IIIb−/− mutant mouse embryos is preceded by endodermal apoptosis and involution of the surrounding mesoderm. We have observed that involution of the atretic segment is preceded by down regulation of Sonic hedgehog (SHH) in the endoderm which is a critical organizer of the intestinal mesoderm. We hypothesized that supplementation of Fgfr2IIIb−/− intestinal tracts with exogenous SHH protein prior to atresia formation would prevent involution of the mesoderm and rescue normal intestinal development. In situ hybridization were performed on control and Fgfr2IIIb−/− intestinal tracts for Shh or FoxF1 between embryonic (E) day 11.5 and E12.0. Control and Fgfr2IIIb−/− intestinal tracts were harvested at E10.5 and cultured in media supplemented with FGF10 + SHH, or FGF10 with a SHH-coated bead. In situs were performed at E12.5 for Foxf1. Shh and Foxf1 expression were down-regulated during intestinal atresia formation. Media containing exogenous FGF10 + SHH did not prevent colonic atresia formation (involution). A SHH protein point source bead did induce Foxf1 expression in controls and mutants. Shh and Foxf1 expression are disrupted in atresia formation of distal colon, thereby serving as potential markers of atretic events. Application of exogenous SHH (in media supplement or as a point source bead) is sufficient to induce Foxf1 expression but insufficient to rescue development of distal colonic mesoderm in Fgfr2IIIb−/− mutant embryos. Shh signal disruption is not the critical mechanism by which loss of Fgfr2IIIb function results in atresia formation.
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影响因子：
2.4
作者：
Nichol, Peter F.;Botham, Robert;Saijoh, Yukio;Reeder, Amy L.;Zaremba, Krzyztoff M.
通讯作者：
Zaremba, Krzyztoff M.
影响因子：
4.8
作者：
Madison, Blair B.;McKenna, Lindsay B.;Kaestner, Klaus H.
通讯作者：
Kaestner, Klaus H.
影响因子：
2.4
作者：
Fairbanks, TJ;Kanard, RC;Burns, RC
通讯作者：
Burns, RC
影响因子：
1.5
作者：
Tang, SHE;Silva, FJ;Mann, JR
通讯作者：
Mann, JR
Fgfr2IIIb-/- 小鼠肠闭锁的形成与脊索发育缺陷或 Shh 表达改变无关。
DOI：
10.1016/j.jss.2012.04.024
发表时间：
2012-09
期刊：
The Journal of surgical research
影响因子：
--
作者：
Reeder AL;Botham RA;Franco M;Zaremba KM;Nichol PF
通讯作者：
Nichol PF